Figure 7. Bevacizumab induces vessel co-option to mediate treatment resistance in CRCLM patients.

(A) CT scan images of CRCLM patients with DHGP or PHGP treated preoperatively with Chemo or Bev+Chemo, and red arrows indicate the tumor lesions. Quantification of the morphologic response to RHGP is shown. (B) H&E staining of the tumor-liver interface of human CRCLM tissues. Quantification of RHGP is shown (n = 6). Scale bar: 100 μm. (C) Immunohistochemical staining of FGFBP1 in the tumor-liver interface of human CRCLM tissues. Scale bar: 20 μm. Quantification of FGFBP1 staining is shown (right panel, n = 6). (D) Immunofluorescence staining of the EpCAM⁺ cancer cells (green) that infiltrated the liver parenchyma and hijacked the CD31⁺ sinusoidal blood vessels (red), and FAPα (gray) expression in the co-opted HSCs in the tumor-liver interface of human CRCLM tissues. Scale bar: 20 μm. Quantification of the co-opted sinusoidal blood vessels and FAPα⁺ HSCs is shown (n = 6). Yellow arrows indicate the FAPα⁺ HSCs. (E) Immunofluorescence staining of p-FGFR1(green) in HSCs attached to the CD31⁺ sinusoidal blood vessels (red) in the tumor-liver interface of human CRCLM tissues. Scale bar: 20 μm. White arrows indicate the p-FGFR1⁺ HSCs. (F) Pearson’s correlation analysis of FAPα⁺ HSCs and the co-opted sinusoidal blood vessels, percentage of RHGP, or FGFBP1 expression in human CRCLM tissues (n = 82). (G) CT scan images of CRCLM patients with RHGP treated preoperatively with Chemo or Bev+Chemo, and red arrows indicate the tumor lesions. Quantification of the change of tumor burden is shown. Dotted lines indicate the tumor-liver interface. Chemo, chemotherapy; Bev, bevacizumab; T, tumor; L, liver. Data are presented as mean ± SEM. NS, no significance. **P < 0.01, ***P < 0.001 (2-tailed, unpaired t test).